A novel PAA derivative with enhanced drug efficacy in pancreatic cancer cell lines.

Alsuraifi, Ali; Kong Thoo Lin, Paul; Curtis, Anthony; Lamprou, Dimitrios A.; Hoskins, Clare

Abstract

Nanoparticles have been shown to be effective drug carriers in cancer therapy. Pancreatic cancer forms dense tumours which are often resistant to drug molecules. In order to overcome such multidrug resistance, new drug entities, novel delivery systems and combination therapy strategies are being explored. In this paper, we report the design and synthesis of a poly(allylamine)-based amphiphile modified with hydrophobic naphthalimido pendant groups. Bisnaphthalimide compounds have been shown to possess anticancer activity. The potential of this polymer to encapsulate, solubilize and enhance drug (5-fluorouricil and bis-(naphthalimidopropyl)-diaminooctane) cytotoxicity in BxPC-3 cells was evaluated. Our studies showed that the insoluble drugs could be formulated up to 4.3 mg mL−1 and 2.4 mg mL−1 inside the amphiphiles, respectively. Additionally, the novel poly(allylamine)-naphthalimide carrier resulted in an amplification of cytotoxic effect with drug treatment after 24 h, and was capable of reduction of 50% cell population at concentrations as low as 3 μg mL−1.

Citation

ALSURAIFI, A., KONG THOO LIN, P., CURTIS, A., LAMPROU, D.A. and HOSKINS, C. 2018. A novel PAA derivative with enhanced drug efficacy in pancreatic cancer cell lines. Pharmaceuticals [online], 11(4), article ID 91. Available from: https://doi.org/10.3390/ph11040091

• Journal Article Type: Article
• Acceptance Date: Sep 19, 2018
• Online Publication Date: Sep 22, 2018
• Publication Date: Dec 31, 2018
• Deposit Date: Oct 15, 2018
• Publicly Available Date: Oct 15, 2018
• Journal: Pharmaceuticals
• Electronic ISSN: 1424-8247
• Publisher: MDPI
• Peer Reviewed: Peer Reviewed
• Volume: 11
• Issue: 4
• Article Number: 91
• DOI: https://doi.org/10.3390/ph11040091
• Keywords: Nanomedicine; Nanopharmaceutics; Drug solubilisation; Pancreatic cancer; Bisnaphthalimide
• Public URL: http://hdl.handle.net/10059/3168
• Contract Date: Oct 15, 2018